Lysyl oxidase-dependent extracellular matrix crosslinking modulates calcification in atherosclerosis and aortic valve disease

Atherosclerosis; Cardiovascular calcification; Lysyl oxidase

Detalles Bibliográficos
Autores: Cañes Esteve, Laia, Vázquez-Sufuentes, Paula, Fernandez-Celis, Amaya, Ballester-Servera, Carme, Alonso Nieto, Judith, Puertas-Umbert, Lidia, Rodriguez-Sinovas, Antonio
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Institución:Departament de Salut de la Generalitat de Catalunya (DS)
Repositorio:Scientia. Dipòsit d'Informació Digital del Departament de Salut
OAI Identifier:oai:scientiasalut.gencat.cat:11351/10378
Acceso en línea:https://hdl.handle.net/11351/10378
Access Level:acceso abierto
Palabra clave:Matriu extracel·lular
Arteriosclerosi
Vasos sanguinis - Calcificació
ANATOMY::Cells::Cellular Structures::Extracellular Space::Extracellular Matrix
DISEASES::Cardiovascular Diseases::Vascular Diseases::Arterial Occlusive Diseases::Arteriosclerosis::Atherosclerosis
DISEASES::Nutritional and Metabolic Diseases::Metabolic Diseases::Calcium Metabolism Disorders::Calcinosis::Vascular Calcification
ANATOMÍA::células::estructuras celulares::espacio extracelular::matriz extracelular
ENFERMEDADES::enfermedades cardiovasculares::enfermedades vasculares::arteriopatías oclusivas::arteriosclerosis::aterosclerosis
ENFERMEDADES::enfermedades nutricionales y metabólicas::enfermedades metabólicas::trastornos del metabolismo del calcio::calcinosis::calcificación vascular
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oai_identifier_str oai:scientiasalut.gencat.cat:11351/10378
network_acronym_str ES
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repository_id_str
dc.title.none.fl_str_mv Lysyl oxidase-dependent extracellular matrix crosslinking modulates calcification in atherosclerosis and aortic valve disease
title Lysyl oxidase-dependent extracellular matrix crosslinking modulates calcification in atherosclerosis and aortic valve disease
spellingShingle Lysyl oxidase-dependent extracellular matrix crosslinking modulates calcification in atherosclerosis and aortic valve disease
Cañes Esteve, Laia
Matriu extracel·lular
Arteriosclerosi
Vasos sanguinis - Calcificació
ANATOMY::Cells::Cellular Structures::Extracellular Space::Extracellular Matrix
DISEASES::Cardiovascular Diseases::Vascular Diseases::Arterial Occlusive Diseases::Arteriosclerosis::Atherosclerosis
DISEASES::Nutritional and Metabolic Diseases::Metabolic Diseases::Calcium Metabolism Disorders::Calcinosis::Vascular Calcification
ANATOMÍA::células::estructuras celulares::espacio extracelular::matriz extracelular
ENFERMEDADES::enfermedades cardiovasculares::enfermedades vasculares::arteriopatías oclusivas::arteriosclerosis::aterosclerosis
ENFERMEDADES::enfermedades nutricionales y metabólicas::enfermedades metabólicas::trastornos del metabolismo del calcio::calcinosis::calcificación vascular
title_short Lysyl oxidase-dependent extracellular matrix crosslinking modulates calcification in atherosclerosis and aortic valve disease
title_full Lysyl oxidase-dependent extracellular matrix crosslinking modulates calcification in atherosclerosis and aortic valve disease
title_fullStr Lysyl oxidase-dependent extracellular matrix crosslinking modulates calcification in atherosclerosis and aortic valve disease
title_full_unstemmed Lysyl oxidase-dependent extracellular matrix crosslinking modulates calcification in atherosclerosis and aortic valve disease
title_sort Lysyl oxidase-dependent extracellular matrix crosslinking modulates calcification in atherosclerosis and aortic valve disease
dc.creator.none.fl_str_mv Cañes Esteve, Laia
Vázquez-Sufuentes, Paula
Fernandez-Celis, Amaya
Ballester-Servera, Carme
Alonso Nieto, Judith
Puertas-Umbert, Lidia
Rodriguez-Sinovas, Antonio
author Cañes Esteve, Laia
author_facet Cañes Esteve, Laia
Vázquez-Sufuentes, Paula
Fernandez-Celis, Amaya
Ballester-Servera, Carme
Alonso Nieto, Judith
Puertas-Umbert, Lidia
Rodriguez-Sinovas, Antonio
author_role author
author2 Vázquez-Sufuentes, Paula
Fernandez-Celis, Amaya
Ballester-Servera, Carme
Alonso Nieto, Judith
Puertas-Umbert, Lidia
Rodriguez-Sinovas, Antonio
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Institut Català de la Salut
[Ballester-Servera C, Alonso J, Cañes L] Instituto de Investigaciones Biomédicas de Barcelona-Consejo Superior de Investigaciones Científicas (IIBB-CSIC), Barcelona, Spain. CIBER de Enfermedades Cardiovasculares, Instituto de Salud Carlos III, Madrid, Spain. Institut d’Investigació Biomèdica Sant Pau (IIB SANT PAU), Barcelona, Spain. [Vázquez-Sufuentes P] Instituto de Investigaciones Biomédicas de Barcelona-Consejo Superior de Investigaciones Científicas (IIBB-CSIC), Barcelona, Spain. Institut d’Investigació Biomèdica Sant Pau (IIB SANT PAU), Barcelona, Spain. [Puertas-Umbert L] CIBER de Enfermedades Cardiovasculares, Instituto de Salud Carlos III, Madrid, Spain. Institut d’Investigació Biomèdica Sant Pau (IIB SANT PAU), Barcelona, Spain. Institut de Recerca Hospital de la Santa Creu i Sant Pau (IRHSCSP), Barcelona, Spain. [Fernández-Celis A] Cardiovascular Translational Research, Navarrabiomed, IdiSNA, UPNA, Hospital Universitario de Navarra (HUN), Pamplona, Spain. [Rodríguez-Sinovas A] CIBER de Enfermedades Cardiovasculares, Instituto de Salud Carlos III, Madrid, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. Grup de Recerca de Malalties Cardiovasculars, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain
Vall d'Hebron Barcelona Hospital Campus
dc.subject.none.fl_str_mv Matriu extracel·lular
Arteriosclerosi
Vasos sanguinis - Calcificació
ANATOMY::Cells::Cellular Structures::Extracellular Space::Extracellular Matrix
DISEASES::Cardiovascular Diseases::Vascular Diseases::Arterial Occlusive Diseases::Arteriosclerosis::Atherosclerosis
DISEASES::Nutritional and Metabolic Diseases::Metabolic Diseases::Calcium Metabolism Disorders::Calcinosis::Vascular Calcification
ANATOMÍA::células::estructuras celulares::espacio extracelular::matriz extracelular
ENFERMEDADES::enfermedades cardiovasculares::enfermedades vasculares::arteriopatías oclusivas::arteriosclerosis::aterosclerosis
ENFERMEDADES::enfermedades nutricionales y metabólicas::enfermedades metabólicas::trastornos del metabolismo del calcio::calcinosis::calcificación vascular
topic Matriu extracel·lular
Arteriosclerosi
Vasos sanguinis - Calcificació
ANATOMY::Cells::Cellular Structures::Extracellular Space::Extracellular Matrix
DISEASES::Cardiovascular Diseases::Vascular Diseases::Arterial Occlusive Diseases::Arteriosclerosis::Atherosclerosis
DISEASES::Nutritional and Metabolic Diseases::Metabolic Diseases::Calcium Metabolism Disorders::Calcinosis::Vascular Calcification
ANATOMÍA::células::estructuras celulares::espacio extracelular::matriz extracelular
ENFERMEDADES::enfermedades cardiovasculares::enfermedades vasculares::arteriopatías oclusivas::arteriosclerosis::aterosclerosis
ENFERMEDADES::enfermedades nutricionales y metabólicas::enfermedades metabólicas::trastornos del metabolismo del calcio::calcinosis::calcificación vascular
description Atherosclerosis; Cardiovascular calcification; Lysyl oxidase
publishDate 2023
dc.date.none.fl_str_mv 2023
2023
2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/11351/10378
url https://hdl.handle.net/11351/10378
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Biomedicine & Pharmacotherapy;167
https://doi.org/10.1016/j.biopha.2023.115469
dc.rights.none.fl_str_mv Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv Scientia
reponame:Scientia. Dipòsit d'Informació Digital del Departament de Salut
instname:Departament de Salut de la Generalitat de Catalunya (DS)
instname_str Departament de Salut de la Generalitat de Catalunya (DS)
reponame_str Scientia. Dipòsit d'Informació Digital del Departament de Salut
collection Scientia. Dipòsit d'Informació Digital del Departament de Salut
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869422908472819712
spelling Lysyl oxidase-dependent extracellular matrix crosslinking modulates calcification in atherosclerosis and aortic valve diseaseCañes Esteve, LaiaVázquez-Sufuentes, PaulaFernandez-Celis, AmayaBallester-Servera, CarmeAlonso Nieto, JudithPuertas-Umbert, LidiaRodriguez-Sinovas, AntonioMatriu extracel·lularArteriosclerosiVasos sanguinis - CalcificacióANATOMY::Cells::Cellular Structures::Extracellular Space::Extracellular MatrixDISEASES::Cardiovascular Diseases::Vascular Diseases::Arterial Occlusive Diseases::Arteriosclerosis::AtherosclerosisDISEASES::Nutritional and Metabolic Diseases::Metabolic Diseases::Calcium Metabolism Disorders::Calcinosis::Vascular CalcificationANATOMÍA::células::estructuras celulares::espacio extracelular::matriz extracelularENFERMEDADES::enfermedades cardiovasculares::enfermedades vasculares::arteriopatías oclusivas::arteriosclerosis::aterosclerosisENFERMEDADES::enfermedades nutricionales y metabólicas::enfermedades metabólicas::trastornos del metabolismo del calcio::calcinosis::calcificación vascularAtherosclerosis; Cardiovascular calcification; Lysyl oxidaseAterosclerosis; Calcificación cardiovascular; Lisil oxidasaAterosclerosi; Calcificació cardiovascular; Lisil oxidasaExtracellular matrix (ECM) is an active player in cardiovascular calcification (CVC), a major public health issue with an unmet need for effective therapies. Lysyl oxidase (LOX) conditions ECM biomechanical properties; thus, we hypothesized that LOX might impact on mineral deposition in calcific aortic valve disease (CAVD) and atherosclerosis. LOX was upregulated in calcified valves from two cohorts of CAVD patients. Strong LOX immunostaining was detected surrounding calcified foci in calcified human valves and atherosclerotic lesions colocalizing with RUNX2 on valvular interstitial cells (VICs) or vascular smooth muscle cells (VSMCs). Both LOX secretion and organized collagen deposition were enhanced in calcifying VICs exposed to osteogenic media. β-aminopropionitrile (BAPN), an inhibitor of LOX, attenuated collagen deposition and calcification. VICs seeded onto decellularized matrices from BAPN-treated VICs calcified less than cells cultured onto control scaffolds; instead, VICs exposed to conditioned media from cells over-expressing LOX or cultured onto LOX-crosslinked matrices calcified more. Atherosclerosis was induced in WT and transgenic mice that overexpress LOX in VSMC (TgLOXVSMC) by AAV-PCSK9D374Y injection and high-fat feeding. In atherosclerosis-challenged TgLOXVSMC mice both atherosclerosis burden and calcification assessed by near-infrared fluorescence (NIRF) imaging were higher than in WT mice. These animals also exhibited larger calcified areas in atherosclerotic lesions from aortic arches and brachiocephalic arteries. Moreover, LOX transgenesis exacerbated plaque inflammation, and increased VSMC cellularity, the rate of RUNX2-positive cells and both connective tissue content and collagen cross-linking. Our findings highlight the relevance of LOX in CVC and postulate this enzyme as a potential therapeutic target for CVC.We thank the technical support provided by Silvia Aguiló. This work was supported by the Spanish Ministerio de Ciencia e Innovación (RTI2018-094727-B-100 and PID2021-122509OB-I00 funded by MCIN/ AEI/10.13039/501100011033 and by “ERDF A way of making Europe”), Instituto de Salud Carlos III (ISCIII; Spain; PI21/01048), and Fundación Española de Arteriosclerosis (FEA-2022). C.B-S and L.P-U were supported by a FPU (Ministerio de Universidades; Spain), and PFIS (ISCIII) fellowships, respectively and N.L-A by a Miguel Servet contract (ISCIII). There is no financial or personal relationship with organizations that could potentially influence the described research.ElsevierInstitut Català de la Salut[Ballester-Servera C, Alonso J, Cañes L] Instituto de Investigaciones Biomédicas de Barcelona-Consejo Superior de Investigaciones Científicas (IIBB-CSIC), Barcelona, Spain. CIBER de Enfermedades Cardiovasculares, Instituto de Salud Carlos III, Madrid, Spain. Institut d’Investigació Biomèdica Sant Pau (IIB SANT PAU), Barcelona, Spain. [Vázquez-Sufuentes P] Instituto de Investigaciones Biomédicas de Barcelona-Consejo Superior de Investigaciones Científicas (IIBB-CSIC), Barcelona, Spain. Institut d’Investigació Biomèdica Sant Pau (IIB SANT PAU), Barcelona, Spain. [Puertas-Umbert L] CIBER de Enfermedades Cardiovasculares, Instituto de Salud Carlos III, Madrid, Spain. Institut d’Investigació Biomèdica Sant Pau (IIB SANT PAU), Barcelona, Spain. Institut de Recerca Hospital de la Santa Creu i Sant Pau (IRHSCSP), Barcelona, Spain. [Fernández-Celis A] Cardiovascular Translational Research, Navarrabiomed, IdiSNA, UPNA, Hospital Universitario de Navarra (HUN), Pamplona, Spain. [Rodríguez-Sinovas A] CIBER de Enfermedades Cardiovasculares, Instituto de Salud Carlos III, Madrid, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. Grup de Recerca de Malalties Cardiovasculars, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, SpainVall d'Hebron Barcelona Hospital Campus202320232023info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttps://hdl.handle.net/11351/10378Scientiareponame:Scientia. Dipòsit d'Informació Digital del Departament de Salutinstname:Departament de Salut de la Generalitat de Catalunya (DS)InglésBiomedicine & Pharmacotherapy;167https://doi.org/10.1016/j.biopha.2023.115469Attribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:scientiasalut.gencat.cat:11351/103782026-06-12T09:38:37Z
score 15,81155

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